Citric Acid → tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To an oven-dried 500-mL 3-neck flask purged with nitrogen was added oxalyl chloride (5.32 mL, 60.8 mmol) and anhydrous dichloromethane (125 mL), and the solution cooled to −78° C. A solution of anhydrous DMSO (7.30 mL, 103 mmol) in anhydrous dichloromethane (25 mL) was added dropwise from a constant-pressure addition funnel over 20-min period. A solution of (S)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (9.41 g, 46.8 mmol) in anhydrous dichloromethane (50 mL) was added dropwise from a constant-pressure addition funnel over 20-min period, then stirred reaction mixture at −78° C. for 30 min. Added triethylamine (32.6 mL, 234 mmol) dropwise via syringe over a 5-min period and stirred the thick white mixture in an ice-water bath for 30 min. Quenched reaction with 10% (w/v) aq. citric acid (30 mL), poured reaction into a separatory funnel with Et2O (550 mL) and 10% (w/v) aq citric acid, separated layers, and washed organic phase with water and brine. Dried the organic phase over anhydrous Na2SO4, filtered, and concentrated to afford a yellow oil (9.4 g), which was used directly in the next reaction.

Provenance & Evidence